Glycerophosphatidylcholine PC(36:1) absence and 3′-phosphoadenylate (pAp) accumulation are hallmarks of the human glioma metabolome

Li, Wenchen; Jia, Hongmei; Li, Qi; Cui, Jiayue; Li, Ri; Zou, Zhong‐Mei; Hong, Xinyu

doi:10.1038/s41598-018-32847-8

Cited by 10 publications

(9 citation statements)

References 46 publications

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“…Lipid disruptions in gliomas have been reported. Wenchen et al founded PC (36:1) absence in glioma tissues compared to trauma brain tissues, which is considered as a hallmark of human glioma metabolome [18]. In our study, PC (36:1) showed a lower level in glioma tissues than in para-tumor tissues (Table S1).…”

Section: Differential Metabolites Between Glioma and Paired Para-tumosupporting

confidence: 52%

Metabolic Alterations Related to Glioma Grading Based on Metabolomics and Lipidomics Analyses

Xuan

Zhang

et al. 2020

Metabolites

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Gliomas are the most aggressive phenotypes of brain tumors and are classified into four grades according to the malignancy degree by the World Health Organization. Metabolic profiling can provide an overview of metabolic reprogramming at a specific stage of tumor initiation and development. Studies about metabolic alterations related to different grades of gliomas are helpful to understand the molecular mechanism for progression of glioma. In the current study, metabolomics and lipidomics analyses based on chromatography-mass spectrometry were performed on different grades of glioma tissues. Differential metabolites between glioma and para-tumor tissues were studied and used as the basis to explore metabolic alterations related to glioma grading. It was found that short-chain acylcarnitines were elevated, whereas lysophosphatidylethanolamines (LPEs) were decreased in high-grade gliomas. Furthermore, the gene expression of short/branched-chain acyl-coenzyme dehydrogenase (ACADSB), which is involved in fatty acid oxidation, was found down-regulated with glioma progression by analyzing related genes and pathways. In addition, LPE metabolism showed a significant difference among different grades of gliomas. These important metabolic pathways related to glioma progression may provide potential clues for further study on the mechanisms and treatment of glioma.

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Section: Differential Metabolites Between Glioma and Paired Para-tumosupporting

confidence: 52%

Metabolic Alterations Related to Glioma Grading Based on Metabolomics and Lipidomics Analyses

Xuan

Zhang

et al. 2020

Metabolites

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“…Among these genes, the significantly overexpressing bisphosphate nucleotidase-1 (BPNT1) was found to be associated with the abnormality of 3'-phosphoadenylate metabolism in glioma. 16 Decorin (DCN), as a potential biomarker, was reported to be correlated with the prognosis of colon cancer and lung adenocarcinoma. 17,18 In lung cancer, mutation of GDP-mannose pyrophosphorylase A (GMPPA) showed significantly negative association with prognosis of patients.…”

Section: Histological Gradementioning

confidence: 99%

Development and Validation of a Scoring System Based on 9 Glycolysis-Related Genes for Prognosis Prediction in Gastric Cancer

Luo

Duan

et al. 2020

Technol Cancer Res Treat

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Gastric cancer is a malignant tumor with high morbidity and mortality worldwide. However, increasing evidences have revealed the correlation between the glycolysis process and tumorigenesis. This study is aim to develop a list of glycolysis-related genes for risk stratification in gastric cancer patients. We included 500 patients’ sample data from GSE62254 and GSE26942 datasets, and classified patients into training (n = 350) and testing sets (n = 150) at a ratio of 7: 3. Univariate and multivariate Cox regression analysis were performed to screen genes having prognostic value. Based on HALLMARK gene sets, we identified 9 glycolysis-related genes (BPNT1, DCN, FUT8, GMPPA, GPC3, LDHC, ME2, PLOD2, and UGP2). On the basis of risk score developed by the 9 genes, patients were classified into high- and low-risk groups. The survival analysis showed that the high-risk patients had a worse prognosis ( p < 0.001). Similar finding was observed in the testing cohort and 2 independent cohorts (GSE13861 and TCGA-STAD, all p < 0.001). The multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for overall survival ( p < 0.001). Furthermore, we constructed a nomogram that integrated the risk score and tumor stage, age, and adjuvant chemotherapy. Through comparing the results of the receiver operating characteristic curves and decision curve analysis, we found that the nomogram had a superior predictive accuracy than conventional TNM staging system, suggesting that the risk score combined with other clinical factors (age, tumor stage, and adjuvant chemotherapy) can develop a robust prediction for survival and improve the individualized clinical decision making of the patient. In conclusion, we identified 9 glycolysis-related genes from hallmark glycolysis pathway. Based on the 9 genes, gastric cancer patients were separated into different risk groups related to survival.

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“…IMPAD1, an inositol phosphatase protein, can catalyse inositol–phosphate hydrolysis to inositol and phosphoadenosine–phosphate hydrolysis to adenosine monophosphate. 31 IMPAD1 gene mutation leads to joint cartilage dysplasia 32 and Catel–Manzke syndrome. 33 Aberrant overexpression of IMPAD1 was observed in breast cancer with Myc oncogene co‐amplification, 34 but the precise role of IMPAD1 in cancer is still unknown.…”

Section: Discussionmentioning

confidence: 99%

LncRNA BC promotes lung adenocarcinoma progression by modulating IMPAD1 alternative splicing

Chen

Cai

Yang

et al. 2023

Clinical & Translational Med

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Background The therapeutic value of targeted therapies in patients with lung cancer is reduced when tumours acquire secondary resistance after an initial period of successful treatment. However, the molecular events behind the resistance to targeted therapies in lung cancer remain largely unknown. Aims To discover the important role and mechanism of lncRNA BC in promoting tumor metastasis and influencing clinical prognosis of LUAD. Materials & Methods: Microarrays were used to screen a comprehensive set of lncRNAs with differential expression profiles in lung cancer cells. The functional role and mechanism of lncRNA were further investigated by gain‐ and loss‐of‐function assays. RNA pull‐down, protein assays, and mass spectrometry were used to identify proteins that interacted with lncRNA. TaqMan PCR was used to measure lncRNA in lung adenocarcinoma and adjacent nontumor tissues from 428 patients. The clinical significance of lncRNA identified was statistically confirmed in this cohort of patients. Results In this study, we show that the long non‐coding RNA BC009639 (BC) is involved in acquired resistance to EGFR‐targeted therapies. Among the 235 long non‐coding RNAs that were differentially expressed in lung cancer cell lines, with different metastatic potentials, BC promoted growth, invasion, metastasis, and resistance to EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs), both in vitro and in vivo. BC was highly expressed in 428 patients with lung adenocarcinoma (LUAD) and high BC expression correlated with reduced efficacy of EGFR‐TKI therapy. To uncover the molecular mechanism of BC‐mediated EGFR‐TKI resistance in lung cancer, we screened and identified nucleolin and hnRNPK that interact with BC. BC formed the splicing complex with nucleolin and hnRNPK to facilitate the production of a non‐protein‐coding inositol monophosphatase domain containing 1 (IMPAD1) splice variant, instead of the protein‐coding variant. The BC‐mediated alternative splicing (AS) of IMPAD1 resulted in the induction of the epithelial–mesenchymal transition and resistance to EGFR‐TKI in lung cancer. High BC expression correlated with clinical progress and poor survival among 402 patients with LUAD. Disscussion Through alternative splicing, BC boosted the non‐coding IMPAD1‐203 transcript variant while suppressing the IMPAD1‐201 variant. In order to control the processing of pre‐mRNA, BC not only attracted RNA binding proteins (NCL, IGF2BP1) or splicing factors (hnRNPK), but also controlled the formation of the splicing‐regulator complex by creating RNA‐RNA‐duplexes. Conclusion Our results reveal an important role for BC in mediating resistance to EGFR‐targeted therapy in LUAD through IMPAD1 AS and in implication for the targeted therapy resistance.

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Glycerophosphatidylcholine PC(36:1) absence and 3′-phosphoadenylate (pAp) accumulation are hallmarks of the human glioma metabolome

Cited by 10 publications

References 46 publications

Metabolic Alterations Related to Glioma Grading Based on Metabolomics and Lipidomics Analyses

Metabolic Alterations Related to Glioma Grading Based on Metabolomics and Lipidomics Analyses

Development and Validation of a Scoring System Based on 9 Glycolysis-Related Genes for Prognosis Prediction in Gastric Cancer

LncRNA BC promotes lung adenocarcinoma progression by modulating IMPAD1 alternative splicing

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